September 04, 2007

Freeing our genomes

J. Craig Venter, one of the original competitors in the race to sequence the human genome, has sequenced and published his own DNA, the first time a single individual's genome has been sequenced.

In the New York Times, Nicholas Wade does a good job with the story, focusing on the original race between the academic consortium and Venter's then-company, Celera. The academic consortium won that race, and the first draft copy of the human genome sequence was public domain -- not privately owned, as Celera's version would have been. Venter left Celera and started a new institute (named for himself) and set out to sequence a single individual's DNA (his own). His success today is being portayed as a Return of the Jedi moment, with Venter in the hero's role. But to me, today's news is a big win for Venter, but an even bigger victory for public science.

Consider: Venter published the DNA sequence itself free, to the public, with no restrictions on its use. It's been deposited in the free, public DNA database at the government-funded National Center for Biotechnology Information, part of the NIH. He's going to publish, for free, his own medical records for researchers to compare his genetics and his health. And the paper itself was published in Public Library of Science (PLoS), an upstart journal begun a few years ago with the aim of overturning the subscription-only stranglehold of the Elsevier publishing empire, and hoping to become an Open Access journal of the same caliber as the subscription-only Science, Nature, and Cell.

As a result, you own his genome. You can read the original paper, free, the day it is published (today). If you're not in the field, you can read an editor's summary, written just for you, also free. There's a free interactive poster (PDF) for you to play with, and you can even access the raw data of the original shotgun sequencing reads, if you ever wanted to.

Venter gets the last word, but ultimately it's public science over privatized science that has won out. What's a real shame is that he had to raise money for this privately, because the NIH pocketbook is too tight to fund even a project of such monumental importance (and there were other issues too). Good for Venter for giving back to the public more than he was given.

Comments

Yeah, I agree with you about Venter here; which is somewhat of a surprise as I considered him somewhat of a villian in the original race. Here in Phoenix, we keep abreast of these things (or at least I do because of some study of genetics long ago in college) because of the work of the Translational Genomics Center (TGEN) here. Nice piece here Pockets.

I am not sure I follow this. What happened to the open access (and presumably free access) to the original academic consortium's Human Genome Project database?
Or is Venter's freely provided personal medical history the additional benefit to using his data?

I was not aware Elsevier has a stranglehold on the publishing world. Could you explain that more fully? Is Elsevier interfering with the free flow of science? Which subscriptions does it control?

As for free vs pay-per view, many med and science journals require subscription to read science advances. Some, like New England Journal of medicine, do frees tories about bird flu because of compelling benefit to society, but otherwise you pay to see.

lizard, his institute certainly could have retained the rights to any results it generated, including his genome sequence. But by publishing it in an open access journal and depositing it with NCBI, he's giving it out to the public. (The question of patenting DNA -- or even organisms -- is a total mess. For this case, suffice it to say that once something is published it is no longer patentable.)

pdaly, the academic consortium's sequence is still available, but Venter's is a step above. Briefly, the first genome sequence was a composite of many individuals' DNA. What's really exciting about Venter's is that for the first time we can see how much variation there is within a single individual (how many sequence differences are there between the two copies of your chromosomes -- the copy you got from your mother vs the copy you got from your father). That is a fundamental question of huge importance. There are also technical issues -- the "quality" of this new sequence may be higher than what the consortium generated back then -- but the overwhelming issue is the insight into how much variation there is within one of us.

Elsevier is a huge publishing house that owns many of the top-tier journals (and many of the lower-tier ones as well). They have fairly draconian copyright rules, requiring authors to sign over copyright to Elsevier and charging high susbcription or per-article fees. They also are really trying to squeeze university libraries by charging exorbitant subscription fees or only making the desirable journals available as part of expensive "bundles" with a lot of less-desirable journals. All of this is galling because almost every paper published in these journals is paid for with public money, and the results rightfully belong to the public. Not only are they not available, but NIH grant dollars are then being used AGAIN to allow other researchers to read the results of what their fellow NIH-funded scientists have done. PLoS really threw down the gauntlet with open access, but Elsevier (and Nature and Science) still have tight hold on the top-tier journals -- although PLoS is rapidly ascending, and other journals are switching to partial open access models in which certain papers are publicly available or in which all material becomes open access after 6 months or so. It is a big fight within the scientific community to dismantle Elsevier and promote open access. Congress has tried (and succeeded?) to require all NIH-funded papers to be deposited in an open access database, but this hasn't really happened and frankly I'd prefer the power to publish was left with scientists. There was an interesting editorial, reply, and counter-reply on this topic last month in the Journal of Cell Biology, regarding one of the top private philanthropic science funding agencies, Howard Hughes Medical Institute, and its policy on open access publishing. It's a good place to start to get a sense of the debate.

DemFromCT, the NYT piece says "in January 2002, Dr. Venter was abruptly fired as president of Celera" but I have forgotten -- or never knew -- the particulars...

Is Venter's DNA sequence, by itself, all that informative? It's just a piece of the data we need to make such sequencing useful, because we need to compare hundreds, probably thousands, of such sequences before we can know what the most common sequences are. So we'll need sequences from all of the most common populations, but also the most uncommon and isolated populations -- like the Andamese islands, various peoples of the Caucasus and Dagestan regions, the multitudinous tribes throughout the Americas, Indonesia, Papua/New Guinea, and a huge array of people from Africa, because that's where we have the highest genetic diversity. Then the comparisons can begin to find where genetic variation leads to genetic disability.

In other words, I think the Venter sequence is more valuable as an achievement, or proof of concept, than as a data set. Yes, the data set is useful, but not nearly as useful as it will be once we start getting the 'knockoff versions' from China and everywhere else.

I agree with bmaz. When the first push to sequence the human genome happened, I hated Venter and questioned his motives...especially with the spectre of having the results hidden behind a pay firewall. All of his ventures beyond the human genome had me skeptical, but maybe he has come around.

I am actually now happy that Venter got into the race because it spurred a bunch of technological and technique advances.

If Venter eventually sequences and publishes his mother's DNA, too, the database will be robust if not even more complicated then to navigate.

BTW, which cells do best with DNA sequencing for this purpose? I assume skin cells might have developed too many errors during Venter's lifetime to be an accurate representation of the Venter's original DNA makeup when he was just a newly fertiized egg.

I assume blood cells are more pluripotential and therefore have a more accurate catalog of one's original DNA, but blood cells also are constantly replicating so errors might be accruing.

they used blood cells for this study. the short answer is that they were pooling DNA derived from all his blood cells, so I'd imagine any mutations that one population of cells has picked up would be "averaged out" and not show up in the final result (unless they're overproliferating -- hopefully Venter doesn't have lymphoma).

The longer answer is that most DNA-carrying blood cells are differentiated white (immune) cells that are not pluripotent (fwiw, red blood cells don't have nuclei). the (current) idea is that there are adult stem cells stashed away and "protected" -- a master copy of sorts -- that produce cells like skin or blood that go on to differentiate, divide for relatively short periods, and die. The details of this are hotly debated (try googling "immortal strand hypothesis" for a start on one of the big questions in the news recently). It would be fascinating to know how many mutations different tissues of Venter's have acquired. I suppose one way around it would be to look at cells that are mostly set aside very early and mostly don't divide -- like neurons. But I bet Venter would rather leave his brain to science after he's gone, than while he's still with us!

I'm in the medical field, but the basic sciences have come a long way since my school days.

I remember fondly a lecture during which we watched an old 1970s reenactment of the replication and transcription process of DNA (replete with hirsute hippies in their tied-dyed shirts and flowing robes and capes playing the roles of nucleotides, ribosomes and messenger RNA).

Then today I caught the end of a high def TV broadcast on PBS showing a computer aided recreation of DNA replicating and transcribing. The DNA strands were less hairy this time but just as colorful. The process was truly amazing to behold, as if watching with a pair of glasses hooked up to an electron microscope.

OT: In the PBS broadcast they showed the interior of the Eagle Pub in Cambridge, England. The Eagle is where Watson and Crick celebrated their discovery (with other's help whether or not properly credited) that DNA's structure is a double helix.

Interestingly (to me at least) I was sitting in that same pub a year ago today. I saw my empty table in the background.

pdaly, emptypockets, and all others - I can't remember where I got this from originally (It may even have been a post here), but this video is way cool. pdaly's description of the old video made me think of this. Would like to see this video production process applied to the DNA replication/transcription process. Here is a little blurb explaining it and the url:

The Inner Life of Cells

Specially created for Harvard biology students, this eight-minute computer-animated film reveals the beauty and hidden cycle of intricate organic mechanisms at work at the molecular level. The focus is on how white blood cells respond and react to external stimuli. Everything that you see in this clip, the unusual orchestra of Nuclei, proteins, and lipids, are actions that are taking place right now in your body, in every individual cell. This includes one of the most surprising sequences - the motor protein plodding along on two pod-like feet along a track, carrying behind it a sphere of lipids. As cartoonish as that sequence looks, biologists report it’s an accurate rendering. The film is the work of a group called XVIVO using NewTek LightWave 3D and Adobe After Effects.

bmaz, the video link you provided appears broken.
I searched xvivo via google and found this link. Click on the tiny forward arrow in the right lower corner of the screen if the video does not play immediately.
http://www.xvivo.net/press/harvard_university.htm

The above video shows the immune system in amazing detail. I assume it was an XVIVO animation that was used as well for the "DNA" PBS show I saw today.

pdaly - Is not a link; is a URL that must be copied and pasted into the whatever you call it where you place such things in your browser. Ok, if that didn't let the cat out of the bag; I will just admit it. I am lame; especially on links. Sorry about that; but hey, how much do want out of your local idiot lawyer? What was the name of the PBS show; I would like to catch it and have my daughter watch it as well. Thanks.

No, you are reading my words like a good lawyer. :)
I SHOULD have written: I copied the URL you provided into my 'address bar' and visited that site. On that site the video link is broken.

The PBS show is called simply "DNA."
It appears to be a five part series, the first of which I saw today, subtitled The Secret of Life.

The DNA animation comes at the end of the first part. The history of science is also entertaining. Much delving into the various personalities and social interactions of the scientists involved in the DNA investigation.

I personally find Ventner's 'minimal genome' work, and his wider general study of bacterial genomes, much more exciting than the still ongoing human genome battles. He has endured as an impressive and unique scientist despite the smears he suffered for challenging the academic genome project.

"He has endured as an impressive and unique scientist despite the smears he suffered for challenging the academic genome project."

Venter is not an impressive scientist by any measure, and he didn't "challenge" the human genome project. What he recognized was that intellectual property law might leave an opening for a crafty capitalist like himself to make money by dint of priority alone. He didn't invent the goal, and he didn't invent any new technologies. He threw together a "me too" project in the better-funded private sector, and, as the commentary here demonstrates (e.g. "more pluripotential" [sic] is applauded?), the general public and the media aren't well-informed enough to reject his framing of the issue. Venter is good at generating news about himself, but he doesn't have the chops to make a real contribution to the science.

Given that we have learned much more and to greater future practical advantage in sequencing individual non-human genomes, I really wonder what motivated Venter in sequencing his own genome.